Estrogen replacement therapy has been found to reduce the risk of cardiovascular disease and osteoporosis associated with decreased estrogen levels following menopause. It is the purpose of this Phase I program to demonstrate the feasibility of an injectable, fully biodegradable microcapsule form of estradiol which delivers 60 micrograms of estradiol per day for 90 days and thereby provides estrogen replacement without need for frequent oral or transdermaI administration. A new spray core microfluidized bed process is expected to reduce delivery of residual methylene chloride below 100 micrograms/day. Phase I will prepare and characterize microcapsules by drug and polymer content, residual solvent, size distribution, surface morphology, and estradiol crystallinity before studying delivery and degradation in vitro and in rabbits. Phase II program will then prepare clinical samples, test product stability, submit FDA documentation, and conduct a clinical study of safety and pharmacokinetics.